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Sphingomyelin, one of the main lipid components of biological membranes, is actively involved in various cellular processes such as protein trafficking and signal transduction. In particular, specific lateral domains enriched in sphingomyelin and cholesterol have been proposed to play an important functional role in biomembranes, although their precise(More)
Activation of the contractile machinery in skeletal muscle is initiated by the action-potential-induced release of Ca2+ from the sarcoplasmic reticulum (SR). Several proteins involved in SR Ca2+ release are affected by calmodulin kinase II (CaMKII)-induced phosphorylation in vitro, but the effect in the intact cell remains uncertain and is the focus of the(More)
Identification of early mechanisms that may lead from obesity towards complications such as metabolic syndrome is of great interest. Here we performed lipidomic analyses of adipose tissue in twin pairs discordant for obesity but still metabolically compensated. In parallel we studied more evolved states of obesity by investigating a separated set of(More)
A low level of high density lipoprotein cholesterol (HDL-C) is a powerful risk factor for cardiovascular disease. However, despite the reported key role of apolipo-proteins, specifically, apoA-I, in HDL metabolism, lipid molecular composition of HDL particles in subjects with high and low HDL-C levels is currently unknown. Here lipidomics was used to study(More)
The paradigm of biological membranes has recently gone through a major update. Instead of being fluid and homogeneous, recent studies suggest that membranes are characterized by transient domains with varying fluidity. In particular, a number of experimental studies have revealed the existence of highly ordered lateral domains rich in sphingomyelin and(More)
Using extensive atomistic simulations, we show that there is a single experimentally accessible parameter--the sterol tilt--that can be used to determine a sterol's capability to induce order, and thus to promote, e.g., formation of lipid rafts. The observations also facilitate designing new effective sterols.
Currently, there is no comprehensive model for the dynamics of cellular membranes. The understanding of even the basic dynamic processes, such as lateral diffusion of lipids, is still quite limited. Recent studies of one-component membrane systems have shown that instead of single-particle motions, the lateral diffusion is driven by a more complex,(More)
We describe how membrane proteins diffuse laterally in the membrane plane together with the lipids surrounding them. We find a number of intriguing phenomena. The lateral displacements of the protein and the lipids are strongly correlated, as the protein and the neighboring lipids form a dynamical protein-lipid complex, consisting of approximately 50-100(More)
Structure and dynamics of voltage-gated ion channels, in particular the motion of the S4 helix, is a highly interesting and hotly debated topic in current membrane protein research. It has critical implications for insertion and stabilization of membrane proteins as well as for finding how transitions occur in membrane proteins-not to mention numerous(More)
Calcineurin, a Ca(2+)-calmodulin-dependent protein phosphatase (PP2B) is one of the links between Ca(2+) signals and regulation of gene transcription in cardiac muscle. We studied the Ca(2+) signal specificity of calcineurin activation experimentally and with modelling. In the rat atrial preparation, an increase in pacing frequency increased nuclear(More)